期刊
NEUROSCIENCE LETTERS
卷 584, 期 -, 页码 356-361出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2014.11.007
关键词
Ginseng; Gintonin; LPA receptor; [Ca2+](i) transient; Dopamine; Neurotransmitter release
资金
- Basic Science Research Program [2011-0021144]
- Priority Research Centers Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [2012-0006686]
- BK21 plus project fund
Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand. Gintonin elicits an intracellular calcium concentration [Ca2+](i) transient via activation of LPA receptors and regulates calcium-dependent ion channels and receptors. [Ca2+](i) elevation by neurotransmitters or depolarization is usually coupled to neurotransmitter release in neuronal cells. Little is known about whether gintonin-mediated [Ca2+](i) transients.are also coupled to neurotransmitter release. The PC12 cell line is derived from a pheochromocytoma of the rat adrenal medulla and is widely used as a model for catecholamine release. In the present study, we examined the effects of gintonin on dopamine release in PC12 cells. Application of gintonin to PC12 cells induced [Ca2+](i) transients in concentration-dependent and reversible manners. However, ginsenoside Rg(3), another active ingredient of ginseng, induced a lagged and irreversible [Ca2+](i) increase. The induction of gintonin-mediated [Ca2+](i) transients was attenuated or blocked by the LPA1/3 receptor antagonist Ki16425, a phospholipase C inhibitor, an inositol 1,4,5-triphosphate receptor antagonist, and an intracellular Ca2+ chelator. Repeated treatment with gintonin induced homologous desensitization of [Ca2+](i) transients. Gintonin treatment in PC12 cells increased the release of dopamine in a concentration-dependent manner. Intraperitoneal administration of gintonin to mice also increased serum dopamine concentrations. The present study shows that gintonin-mediated [Ca2+](i) transients are coupled to dopamine release via LPA receptor activation. Finally, gintonin-mediated [Ca2+](i) transients and dopamine release via LPA receptor activation might explain one mechanism of gintonin-mediated inter-neuronal modulation in the nervous system. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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